miR‑146a reduces depressive behavior by inhibiting microglial activation

Area of Science:

• Neuroscience
• Immunology
• Psychiatry

Background:

• Depression is a global mental health issue with unclear origins.
• microRNA-146a (miR-146a) is known to modulate inflammatory responses.
• The specific role of miR-146a in depression pathogenesis is not well understood.

Purpose of the Study:

• To investigate the involvement of miR-146a in depression.
• To explore the therapeutic potential of modulating miR-146a in depression models.

Main Methods:

• Established depression models in mice using lipopolysaccharide and chronic unpredictable mild stress.
• Administered miR-146a mimic and short interfering RNA to depressed mice.
• Assessed depression-like behaviors, pro-inflammatory cytokine levels, and neuroinflammation markers (Iba-1, IRAK1, TRAF6, NF-κB) in the hippocampus and BV-2 cells.

Main Results:

• Depressed mice exhibited reduced sucrose preference and increased immobility, indicative of depressive behaviors.
• miR-146a overexpression significantly ameliorated these depressive behaviors and decreased levels of neuroinflammatory factors (Iba-1, IL-1β, TNF-α, IRAK1, TRAF6, p-NF-κB).
• Conversely, miR-146a silencing exacerbated neuroinflammation, and miR-146a mimic treatment suppressed microglial activation in BV-2 cells.

Conclusions:

• miR-146a plays a crucial role in regulating depression-like behaviors.
• Modulating miR-146a can alleviate depression by inhibiting microglial activation and reducing neuroinflammation.
• miR-146a represents a potential therapeutic target for depression treatment.